Hybrid Model Teaching in the Postepidemic Period: From Nucleic Acid to Antigen for the Fluorescence Analysis of SARS-CoV-2

Owing to the global spread of the coronavirus disease 2019 (COVID-19), education has shifted to distance online learning, whereas some face-to-face courses have been resumed with the improvement of the outbreak prevention and management situation, including a laboratory course for senior undergraduate students in chemical biology. Here, we present an innovative chemical biology experiment covering COVID-19 topics, which was created for third-year undergraduates. The basic principles of two nucleic-acid- and antigen-based diagnostic techniques for SARS-CoV-2 are demonstrated in detail. These experiments are designed to provide students with comprehensive knowledge of COVID-19 and related diagnoses in daily life. Crucially, the biosafety of this experimental manipulation was ensured by using artificial nucleic acids and recombinant protein. Furthermore, an interactive hybrid online-facing teaching model was designed to cover the key mechanism regarding PCR and serological tests of COVID-19. Finally, a satisfactory evaluation was obtained through a questionnaire, and simultaneously, reasonable improvements to the course design were suggested. The proposed curriculum provides all the necessary information for other instructors to create new courses supported by research. © 2023 American Chemical Society and Division of Chemical Education, Inc.

Investigating Factors That Influence College Students' Online Continuous Learning Intention during COVID-19 Epidemic

This study aims to explore university students' continuous intention toward online learning during COVID-19 pandemic. A total of 120 students enrolled in online learning were surveyed to collect their perception of an extended model by adding task value to the expectation-confirmation model. Structural equation modeling was employed to verify the hypotheses proposed in this study. The results indicated that task value and technology usefulness were significant predictors of students' continuous intention toward online learning. More specifically, technology usefulness had a direct impact on students' continuous intention, while students' perceived task value played an indirect role in the prediction of their continuous intention. However, the impacts of both confirmation and satisfaction were not statistically significant on students' continuous intention. The results suggest that practitioners and researchers should pay special attention to the technological usefulness of online learning environments and task value, especially task value, in order to enhance students' retention of online learning. This study would contribute to implications to better design and implement online learning. © 2023 IEEE.

Intelligent medicine and beyond

With the developments of medical artificial intelligence (AI), meta-data analysis, intelligence-aided drug design and discovery, surgical robots and image-navigated precision treatments, intelligent medicine (IM) as a new era evolved from ancient medicine and biomedical medicine, has become an emerging topic and important criteria for clinical applications. It is fully characterized by fundamental research-driven, new-generation technique-directed as well as state-of-the-art paradigms for advanced disease diagnosis and therapy leading to an even broader future of modern medicine. As a fundamental subject and also a practice-oriented field, intelligent medicine is highly trans-disciplinary and cross-developed, which has emerged the knowledge of modern medicine, basic sciences and engineering. Basically, intelligent medicine has three domains of intelligent biomaterials, intelligent devices and intelligent techniques. Intelligent biomaterials derive from traditional biomedical materials, and currently are endowed with multiple functionalities for medical uses. For example, micro-/nanorobots, smart responsive biomaterials and digital drugs are representative intelligent biomaterials which have been already commercialized and applied to clinical uses. Intelligent devices, such as surgical robots, rehabilitation robots and medical powered exoskeleton, are an important majority in the family of intelligent medicine. Intelligent biomaterials and intelligent devices are more and more closely integrated with each other especially on the occasions of intelligence acquisition, remote transmission, AI-aided analysis and management. In comparison, intelligent techniques are internalized in the former two domains and are playing a critical role in the development of intelligent medicine. Representative intelligent techniques of telemedicine, image-navigated surgery, virtual/augmented reality and AI-assisted image analysis for early-stage disease assessments have been employed in nowadays clinical operations which to a large extent relieved medical labors. In the past decades, China has been in the leading groups compared to international colleagues in the arena of intelligent medicine, and a series of eminent research has been clinically translated for practical uses in China. For instance, the first 5G-aided remote surgery has been realized in Fujian Province in January 2019, which for the first time validated their applicability for human uses. The surgical robots have found China as the most vigorous market, and more than 10 famous Chinese companies are developing versatile surgical robots for both Chinese people and people all over the world. China also applied AI techniques to new drug developments especially in early 2020 when COVID-19 epidemic roared, and several active molecules and drug motifs have been discovered for early-stage COVID-19 screening and treatments. Based on the significance of intelligent medicine and its rapid developments in both basic research and industrials, this review summarized the comprehensive viewpoints of the Y6 Xiangshan Science Conferences titled with Fundamental Principles and Key Technologies of Intelligent Medicine, and gave an in-depth discussion on main perspectives of future developments of the integration of biomaterial and devices, the integration of bioinformatics and medical hardware, and the synergy of biotechnology and intelligence information. It is expected that this featuring article will further promote intelligent medicine to an even broader community not only for scientists but also for industrials, and in the long run embrace a perspective future for its blooming and rich contributions in China in the coming 5 years.

Investigation on the core competency of residents during Coronavirus disease 2019 outbreak.

Objective To investigate the impact of the outbreak of coronavirus disease 2019 (COVID-19) as an intervention factor on residency training at different stages, and look into the enhancement effect of post-graduation medical training program based on competency of residency training, so as to provide reference for the optimization of medical education at the postgraduate stage. Methods After the initial success of COVID-19 prevention and control, 169 clinical postdoctoral trainess(clinical postdocs) and 515 graduate students specializing in clinical medicine(professional postdocs) were surveyed by an anonymous online questionnaire. To analyze the differences of cognition and self- evaluation of core competence between the two groups. Results There were 141 valid questionnaires collected from clinical postdocs (83.43%, 141/169) and 264 valid questionnaires collected from professional postdocs (51.26%, 264/515). In both groups, more than 85% of the students agreed or strongly agreed that they had a deeper understanding of the profession of doctors during the epidemic. The results of competency self-evaluation showed that, except for the items of "self-improvement", the self-evaluation scores of clinical postdoctoral students on other items were significantly higher than those of professional postdoctoral students (all P <0.05). Conclusions COVID-19, as a factor of emergency intervention, can improve the competency cognition of residents. The core-competency based post-graduation medical education model can comprehensively improve the students' comprehensive ability, which is an effective training program for residents. It is suggested that the vocational planning education for residents should be paid attention to in the stage of college education, and a new mode of college education that is closely combined with the post-graduation education should be further explored.Copyright © 2021 Thomson Reuters and Contributors.

THE SPIKE OF SARS-CoV-2 VARIANTS ALLOWS FOR MORE EFFICIENT COUNTERACTION OF BST2

Background: BST2/Tetherin is an interferon-stimulated gene with antiviral activity against enveloped viruses. Particularly, BST2 tethers virions at their site of assembly, preventing their release and spread. In addition to this primary role, BST2 is as an important bridge between the innate and adaptive immune system, since (i) BST2 routes tethered particles to lysosomes, which generates viral breakdown products that engage pattern recognition receptors;and (ii) trapped virions facilitate antibody-dependent cell-mediated cytotoxicity (ADCC). In turn, viruses have evolved mechanisms to bypass BST2, either by targeting BST2 for proteasomal/lysosomal degradation or by removing BST2 from sites of virion assembly. However, the role of BST2 in SARS-CoV-2 replication, spread, evolution, and pathogenesis remains largely unknown. Method(s): The antiviral potential of BST2 against SARS-CoV-2 was investigated by infecting different SARS-CoV-2 isolates (Hong Kong, Alpha, Beta, Delta, and Omicron) in BST2+ and BST2- cells. Culture supernatants were collected to assess virion production by ELISA and infectivity by TCID50. Infected cells were analyzed by western blot and flow cytometry to examine viral and cellular protein levels, including BST2. Transfection of individual SARS-CoV-2 ORFs and mutagenesis studies allowed us to identify the genes that the virus uses to downregulate BST2. Immunoprecipitation assays revealed protein-protein interactions and changes in ubiquitination patterns. Experiments with proteasomal and lysosomal inhibitors furthered our mechanistic understanding of how SARS-CoV-2 counteracts BST2. Finally, fluorescence microscopy studies uncovered changes in the subcellular distribution of BST2 in SARS-CoV-2 infected cells. Result(s): While BST2 reduces virion release, SARS-CoV-2 has evolved to counteract this effect. Specifically, SARS-CoV-2 uses the Spike to interact with BST2, sequester the protein at perinuclear locations, and ultimately route it for lysosomal degradation. By surveying different SARS-CoV-2 variants of concern (Alpha-Omicron), we found that each variant is more efficient than the previously circulating strain at downregulating BST2 and facilitating virion production, and that mutations in the Spike account for their enhanced BST2 antagonism. Conclusion(s): As part of its adaptation to humans, SARS-CoV-2 is improving its capacity to counteract BST2, highlighting that BST2 antagonism is important for SARS-CoV-2 infectivity and transmission.

Intelligent medicine and beyond

With the developments of medical artificial intelligence (AI), meta-data analysis, intelligence-aided drug design and discovery, surgical robots and image-navigated precision treatments, intelligent medicine (IM) as a new era evolved from ancient medicine and biomedical medicine, has become an emerging topic and important criteria for clinical applications. It is fully characterized by fundamental research-driven, new-generation technique-directed as well as state-of-the-art paradigms for advanced disease diagnosis and therapy leading to an even broader future of modern medicine. As a fundamental subject and also a practice-oriented field, intelligent medicine is highly trans-disciplinary and cross-developed, which has emerged the knowledge of modern medicine, basic sciences and engineering. Basically, intelligent medicine has three domains of intelligent biomaterials, intelligent devices and intelligent techniques. Intelligent biomaterials derive from traditional biomedical materials, and currently are endowed with multiple functionalities for medical uses. For example, micro-/nanorobots, smart responsive biomaterials and digital drugs are representative intelligent biomaterials which have been already commercialized and applied to clinical uses. Intelligent devices, such as surgical robots, rehabilitation robots and medical powered exoskeleton, are an important majority in the family of intelligent medicine. Intelligent biomaterials and intelligent devices are more and more closely integrated with each other especially on the occasions of intelligence acquisition, remote transmission, AI-aided analysis and management. In comparison, intelligent techniques are internalized in the former two domains and are playing a critical role in the development of intelligent medicine. Representative intelligent techniques of telemedicine, image-navigated surgery, virtual/augmented reality and AI-assisted image analysis for early-stage disease assessments have been employed in nowadays clinical operations which to a large extent relieved medical labors. In the past decades, China has been in the leading groups compared to international colleagues in the arena of intelligent medicine, and a series of eminent research has been clinically translated for practical uses in China. For instance, the first 5G-aided remote surgery has been realized in Fujian Province in January 2019, which for the first time validated their applicability for human uses. The surgical robots have found China as the most vigorous market, and more than 10 famous Chinese companies are developing versatile surgical robots for both Chinese people and people all over the world. China also applied AI techniques to new drug developments especially in early 2020 when COVID-19 epidemic roared, and several active molecules and drug motifs have been discovered for early-stage COVID-19 screening and treatments. Based on the significance of intelligent medicine and its rapid developments in both basic research and industrials, this review summarized the comprehensive viewpoints of the Y6 Xiangshan Science Conferences titled with Fundamental Principles and Key Technologies of Intelligent Medicine, and gave an in-depth discussion on main perspectives of future developments of the integration of biomaterial and devices, the integration of bioinformatics and medical hardware, and the synergy of biotechnology and intelligence information. It is expected that this featuring article will further promote intelligent medicine to an even broader community not only for scientists but also for industrials, and in the long run embrace a perspective future for its blooming and rich contributions in China in the coming 5 years. © 2023 Chinese Academy of Sciences. All rights reserved.

Therapeutic Effect of Gegentang Granules on Mouse Model with hCoV-229E Pneumonia and Hanshi Yidu Xifei Syndrome.

Objective:To determine the therapeutic effect of Gegentang granules on a disease-syndrome mouse model combining human coronavirus 229EhCoV-229Epneumonia with Hanshi Yidu Xifei syndrome in vivo. Method(s): Mice were randomly divided into normal group,infection group,cold-dampness group,model group,chloroquine phosphate group0.18 g.kg-1,interferon-alpha2bIFN-alpha2bgroup1.83x106 U.kg-1, Gegentang granules high-dose and low-dose groups6.6,3.3 g.kg-1with 10 mice in each group. Cold-dampness environment and hCoV-229E infection were used for modeling,and the general status and lung index of mice in each group were observed. The viral load in lung tissue was detected by real-time fluorescent quantitative polymerase chain reactionReal-time PCR,the pathological changes in lung tissue were evaluated by hematoxylin-eosinHEstaining,the levels of serum gastrointestinal hormones and inflammatory factors in lung tissue were detected by enzyme-linked immunosorbent assayELISA,and the percentage of peripheral blood lymphocytes was detected by flow cytometry. Result(s):Comparing with model group,Gegentang granules could significantly alleviate the physical signs of Hanshi Yidu Xifei syndrome,including listlessness,weakness of limbs,sticky stool,etc. Comparing with model group,Gegentang granules high-dose group significantly reduced lung index,histopathological score of interstitial lung and bronchus,and the level of serum motilinP< 0.05,P<0.01,two doses of Gegentang granules could significantly increase the level of serum gastrinP< 0.05,P<0.01,the percentage of CD4+ ,CD8+ T lymphocytes in peripheral bloodP<0.05,P<0.01,and the level of tumor necrosis factor-alphaTNF-alphain lung tissue was significantly decreasedP<0.01,and the level of interleukin-6IL-6showed decreasing tendency. Conclusion(s): Gegentang granules has therapeutic effect on model mice. It can improve the appearance and behavior characterization,regulate the level of gastrointestinal hormones,decrease lung index and histopathological score,and possibly play an immunomodulatory role by inhibiting the expression of inflammatory cytokines in lung tissue and restoring the percentage of peripheral blood lymphocytes.Copyright © 2022, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

A Statistical Analysis of the Covid-19 Outbreak Data

The exponential model is a commonly used epidemic model for the analysis of initial outbreak data due to an infectious disease. But there have been questions about its validity in practice. This article examines this issue through statistical analysis on 22 countries' initial COVID-19 outbreak data provided by the World Health Organization. For each of 22 countries, a general regression analysis is conducted for the cumulative confirmed cases. Our regression function is a 3-5 piecewise fitted functions which are obtained via regression analysis

Evaluation Effectiveness of in Vitro Cultivation of Bezoar on Mouse Model Combining Disease with Syndrome of Coronavirus Pneumonia with Yidu Xifei Syndrome.

Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method: BALB/c mice were randomly divided into six groups according to their weight grade:normal group,HCoV-229E infection group,cold and damp group,a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome,and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar (0.128,0.064 g.kg-1 )was administrated by gavage for 3 days from the day of infection. The observation indexes included:general state observation of mice,inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was used to detect the viral load in the lung tissues of mice. Serum levels of motilin(MTL),gastrin(GAS),and cytokines interleukin(IL)-10,IL-6, tumor necrosis factor-alpha(TNF-alpha)and interferon-gamma(IFN-gamma)in lung tissue of mice were determined by enzyme-linked immunosorbent assay(ELISA). The percentages of CD4+ T lymphocytes,CD8+ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group, model group mice lung index increased significantly(P<0.01), nucleic acids significantly increased expression of lung tissue in mice(P<0.01),significantly higher serum MTL content in mice,GAS content significantly decreased(P<0.05,P<0.01),lung tissue cells in the immune factor TNF-alpha,IL-10 and IL-6 were significantly increased(P<0.01),peripheral blood lymphocyte CD4+ T cells in mice,The percentages of CD8+ T cells and B cells were significantly decreased(P<0.01). Compared with model group, in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower(P<0.01),the lung tissue of mice express nucleic acid decreased significantly(P<0.01),MTL content decreased significantly(P< 0.01),the lung tissue of mice in the IL-6,IL-10,the TNF-alpha,IFN-gamma levels were significantly lower(P<0.01), in vitro cultivation bezoar high dose group can significantly increase the CD4+ T cell percentage(P<0.05),in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation,pulmonary interstitial edema,as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice,improving the pathological damage of the lung tissue,adjusting the immune effective and inhibiting the clearing of inflammatory factors,and to provide a laboratory basis for clinical medication.Copyright © 2021, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Early antiviral therapy of abidol combined with lopinavir/ritonavir and recombinant interferon alpha-2b for patients with COVID-19 in Zhejiang: A multicenter prospective study.

Objective: To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon alpha-2b (rIFNalpha-2b) and the combination of lopinavir/ritonavir plus rIFNalpha-2b for patients with COVID-19 in Zhejiang province. Method(s): A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNalpha-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data. Result(s): The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2+/-4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0+/-5.0) d] (t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] (H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively (Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8+/-3.9), (13.5+/-5.1) and (11.2+/-4.3) d, respectively(Z=6.722, P<0.05). Conclusion(s): The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNalpha-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy;and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.Copyright © 2020 by the Chinese Medical Association.

Guidance on the use of biologic agents in psoriatic patients during COVID-19 outbreak.

The COVID-19 outbreak may have some impact on the use of biologics in psoriatic patients because immunosuppressive effects of biologics may potentially alter the susceptibility of patients to the virus, deteriorate the condition of infected patients or even change the prognosis of infection. According to currently available recommendations from international psoriasis academic organizations and specialists, as well as specific situation in China, the authors provide some guidance on the use of biologics for psoriatic patients undergoing or planning to undergo treatment with biologics, those with low or high risk of infection, and for those with or without COVID-19 infection, so as to provide references for clinical practice.Copyright © 2020 by the Chinese Medical Association.

Modeling and Analyzing Online Food Delivery Services Using Design Thinking: An Optimization Approach

The COVID-19 pandemic has significantly strained online food delivery services (OFDS) globally. This has challenged OFDS businesses to redesign and deploy technologies to meet customer demand. The purpose of this article is to identify the optimal factors contributing to customer experience with OFDS services during a black swan event such as the COVID-19 pandemic. We followed a four-step research design to identify the optimal factors for OFDS. First, we identified the major episodes in the OFDS process. Second, these episodes were evaluated by customers using the sequential incidence technique. Third, we used an orthogonal design to analyze the episodes at different levels based on customer preferences. Finally, we used the Taguchi approach to calculate the signal-to-noise ratios and identify the optimal factors and their preferred levels. We classify the optimal factors into customer-oriented and service-provider-oriented propositions. The option to select the delivery person and delivery conditions was found to be the most optimal customer-oriented attribute. We discuss the theoretical and managerial implications of the study and suggest major avenues for digital transformations in OFDS for better customer experience. IEEE

Asthenopia prevalence and vision impairment severity among students attending online classes in low-income areas of western China during the COVID-19 pandemic.

INTRODUCTION: This study explored the impact of online learning during the coronavirus disease 2019 (COVID-19) pandemic on asthenopia and vision impairment in students, with the aim of establishing a theoretical basis for preventive approaches to vision health. METHODS: This balanced panel study enrolled students from western rural China. Participant information was collected before and during the COVID-19 pandemic via questionnaires administered at local vision care centres, along with clinical assessments of visual acuity. Paired t tests and fixed-effects models were used to analyse pandemic-related differences in visual status. RESULTS: In total, 128 students were included (mean age before pandemic, 11.82 ± 1.46 years). The mean total screen time was 3.22 ± 2.90 hours per day during the pandemic, whereas it was 1.97 ± 1.90 hours per day in the pre-pandemic period (P<0.001). Asthenopia prevalence was 55% (71/128) during the pandemic, and the mean visual acuity was 0.81 ± 0.30 logarithm of the minimum angle of resolution; these findings indicated increasing vision impairment, compared with the pre-pandemic period (both P<0.001). Notably, asthenopia prevalence increased by two- to three-fold, compared with the pre-pandemic period. An increase in screen time while learning was associated with an increase in asthenopia prevalence (P=0.034). CONCLUSION: During the COVID-19 pandemic, students spent more time on online classes, leading to worse visual acuity and vision health. Students in this study reported a significant increase in screen time, which was associated with increasing asthenopia prevalence and worse vision impairment. Further research is needed regarding the link between online classes and vision problems.

COVID-19 vaccinations and risk spillovers: Evidence from Asia-Pacific stock markets

This study investigates the impact of COVID-19 vaccinations on volatility (risk) spillovers among major Asia-Pacific stock markets. Utilizing both mean-based and quantile-based connectedness approaches, we examine the evolving patterns and network structure of risk spillovers not only on average but also in the extreme left and right tails. Risk spillovers are typically stronger under extreme shocks. A common regularity observed in the dynamics of standard (average) and extreme risk spillovers is that there are fewer risk spillovers after the launch of the COVID-19 vaccines. We also conduct a series of regression analyses to investigate the association between spillover levels and vaccination rates. The regression results support that an increase in vaccinations is associated with an decrease in standard risk spillovers. Besides, it is observed that vaccinations have an asymmetric impact on the extreme downside-tail and upside-tail risk spillovers. Further, panic sentiment is identified as a potential channel through which vaccinations affect spillovers. Our findings point to the role of COVID-19 vaccinations in stabilizing the Asia-Pacific stock markets by reducing risk spillovers. © 2023 Elsevier B.V.

Evaluation Effectiveness of in Vitro Cultivation of Bezoar on Mouse Model Combining Disease with Syndrome of Coronavirus Pneumonia with Yidu Xifei Syndrome.

Objective:To determine the therapeutic effect of in vitro cultivation of bezoar on a mouse model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. Method: BALB/c mice were randomly divided into six groups according to their weight grade:normal group,HCoV-229E infection group,cold and damp group,a mouse model combining disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome,and high and low dose group of in vitro cultivation of bezoar. The combination model of human coronavirus pneumonia with Yidu Xifei syndrome mice was established by the method of cold dampness condition stimulation+coronavirus HCoV-229E infection. In vitro cultivation of bezoar (0.128,0.064 g.kg-1 )was administrated by gavage for 3 days from the day of infection. The observation indexes included:general state observation of mice,inhibition rate of lung index and lung index of mice. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)was used to detect the viral load in the lung tissues of mice. Serum levels of motilin(MTL),gastrin(GAS),and cytokines interleukin(IL)-10,IL-6, tumor necrosis factor-alpha(TNF-alpha)and interferon-gamma(IFN-gamma)in lung tissue of mice were determined by enzyme-linked immunosorbent assay(ELISA). The percentages of CD4+ T lymphocytes,CD8+ T lymphocytes and B lymphocytes in the blood of mice were determined by flow cytometry. Result:The high and low dose group of in vitro cultivation of bezoar can significantly improve the general condition of model mice. Compared with blank group, model group mice lung index increased significantly(P<0.01), nucleic acids significantly increased expression of lung tissue in mice(P<0.01),significantly higher serum MTL content in mice,GAS content significantly decreased(P<0.05,P<0.01),lung tissue cells in the immune factor TNF-alpha,IL-10 and IL-6 were significantly increased(P<0.01),peripheral blood lymphocyte CD4+ T cells in mice,The percentages of CD8+ T cells and B cells were significantly decreased(P<0.01). Compared with model group, in vitro cultivation bezoar mice lung index of high and low dose group were significantly lower(P<0.01),the lung tissue of mice express nucleic acid decreased significantly(P<0.01),MTL content decreased significantly(P< 0.01),the lung tissue of mice in the IL-6,IL-10,the TNF-alpha,IFN-gamma levels were significantly lower(P<0.01), in vitro cultivation bezoar high dose group can significantly increase the CD4+ T cell percentage(P<0.05),in vitro cultivation bezoar can to a certain extent reduce model mice lung inflammatory exudation,pulmonary interstitial edema,as well as blood stasis symptoms. Conclusion:In vitro cultivation of bezoar has a significant therapeutic effect on a mice model adding disease with syndrome of coronavirus pneumonia with Yidu Xifei syndrome. It can be treated by reducing the lung index of the model mice,improving the pathological damage of the lung tissue,adjusting the immune effective and inhibiting the clearing of inflammatory factors,and to provide a laboratory basis for clinical medication.Copyright © 2021, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Guidance on strengthening the management processes of children's fever in outpatient department during the novel coronavirus pneumonia epidemic period (First Edition).

Novel Coronavirus Pneumonia (NCP) is a class B infectious disease, which is prevented and controlled according to class A infectious diseases. Recently, children's NCP cases have gradually increased, and children's fever outpatient department has become the first strategic pass to stop the epidemic.Strengthening the management of the fever diagnosis process is very important for early detection of suspected children, early isolation, early treatment and prevention of cross-infection. This article proposes prevention and control strategies for fever diagnosis, optimizes processes, prevents cross-infection, health protection and disinfection of medical staff, based on the relevant diagnosis, treatment, prevention and control programs of the National Health and Health Commission and on the diagnosis and treatment experience of experts in various provinces and cities. The present guidance summarizes current strategies on pre-diagnosis;triage, diagnosis, treatment, and prevention of 2019-nCoV infection in common fever, suspected and confirmed children, which provide practical suggestions on strengthening the management processes of children's fever in outpatient department during the novel coronavirus pneumonia epidemic period.Copyright © 2020 by the Chinese Medical Association.

Early antiviral therapy of abidol combined with lopinavir/ritonavir and recombinant interferon alpha-2b for patients with COVID-19 in Zhejiang: A multicenter prospective study.

Objective: To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon alpha-2b (rIFNalpha-2b) and the combination of lopinavir/ritonavir plus rIFNalpha-2b for patients with COVID-19 in Zhejiang province. Method(s): A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNalpha-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data. Result(s): The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2+/-4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0+/-5.0) d] (t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] (H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively (Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8+/-3.9), (13.5+/-5.1) and (11.2+/-4.3) d, respectively(Z=6.722, P<0.05). Conclusion(s): The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNalpha-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy;and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.Copyright © 2020 by the Chinese Medical Association.

Viral and Host Small RNA Response to SARS-CoV-2 Infection

After two years into the pandemic of the coronavirus disease 2019 (COVID-19), it remains unclear how the host RNA interference (RNAi) pathway and host miRNAs regulate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and impact the development of COVID-19. In this study, we profiled small RNAs in SARS-CoV-2-infected human ACE2-expressing HEK293T cells and observed dysregulated host small RNA groups, including specific host miRNAs that are altered in response to SARS-CoV-2 infection. By comparing dysregulated miRNAs in different SARS-CoV-2-infected samples, we identified miRNA-210-3p, miRNA-30-5p, and miR-146a/b as key host miRNAs that may be involved in SARS-CoV-2 infection. Furthermore, by comparing virally derived small RNAs (vsmRNAs) in different SARS-CoV-2-infected samples, we observed multiple hot spots in the viral genome that are prone to generating vsmRNAs, and their biogenesis can be dependent on the antiviral isoform of Dicer. Moreover, we investigated the biogenesis of a recently identified SARS-CoV-2 viral miRNA encoded by ORF7a and found that it is differentially expressed in different infected cell lines or in the same cell line with different viral doses. Our results demonstrate the involvement of both host small RNAs and vsmRNAs in SARS-CoV-2 infection and identify these small RNAs as potential targets for anti-COVID-19 therapeutic development. © 2022 by the authors.